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Table 5 Proposed regulators of VOC

From: Vascular ossification – calcification in metabolic syndrome, type 2 diabetes mellitus, chronic kidney disease, and calciphylaxis – calcific uremic arteriolopathy: the emerging role of sodium thiosulfate

Positive Regulators

Negative Regulators

Minerals: Ca ++ Pi, Phosphate/Pit-1 → Cbfa-1

Fetuin-A

Vitamin D

 

BMP-2

Bone morphogenic protein

MGP

Matrix gammacarboxyglutamate (Gla)-protein

Inhibits BMP-2

Warfarin

 

Warfarin may also cause skin necrosis similar to CPLX via an impairment of Protein C with thrombosis in venules resulting in subcutaneous ischemia and Vitamin K – GLA inhibition.

GLA

gammacarboxyglutamate

Inflammation: TNFalpha, IL-6

IL-10

Oxidized – retained – modified lipids (OxLDL-C, OxVLDL beta lipoproteins) and Low alpha lipoproteins: HDL-C

Osteopontin: OPN

(may be a positive and negative regulator)

ROS

Oxidative-Redox Stress

Osteoprotegerin OPG?

Elevated in human atherosclerosis and CVD yet paradoxically when you have a mouse model with knockout of OPG there is increased osteoporosis and VOC.

A-FLIGHT TOXICITIES (table 3)

 

Glucose

 

Hormones: Insulin, IGF-1, Amylin, Leptin, and PTH

 

I or II Hyperparathyroidism

 

HYPOXIA activates hypoxia inducible factor Hif-1, ROS → Vascular angiogenesis

Vasa Vasorum:

Multipotential → Pericyte

RANK and RANKL

These are involved but as with OPG the entire story is still evolving.

PERICYTE